PTAB

IPR2021-01054

Laboratory Corp Of America Holdings v. Ravgen Inc

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Petition
petition

1. Case Identification

2. Patent Overview

  • Title: METHODS FOR DETECTION OF GENETIC DISORDERS
  • Brief Description: The ’277 patent discloses methods for non-invasive prenatal testing by determining the sequence of a genetic locus of interest on cell-free fetal DNA. The method involves obtaining a sample from a pregnant female that includes an agent selected from a membrane stabilizer, cross-linker, or cell lysis inhibitor to prevent the lysis of maternal cells, thereby reducing background DNA interference.

3. Grounds for Unpatentability

Ground 1: Claims 55-63, 66-69, 80, and 127-132 are obvious over Chiu, Lo, and Bianchi.

  • Prior Art Relied Upon: Chiu (a 2001 article in Clinical Chemistry), Lo (a 1998 article in the American Journal of Human Genetics), and Bianchi (5,648,220).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Chiu and Lo collectively teach determining the sequence of a locus of interest on cell-free fetal DNA from a pregnant female's blood sample. These references describe detecting the SRY gene (fetal-specific) and the β-globin gene (total DNA) using quantitative PCR. However, they lack an explicit teaching of adding a specific agent to inhibit cell lysis. Petitioner contended that Bianchi supplies this missing element by disclosing a method to stabilize fetal cells in maternal blood for genetic analysis. Bianchi teaches using paraformaldehyde to fix the cells, which acts as a cross-linker and membrane stabilizer, thereby preventing cell lysis and preserving cellular DNA. Petitioner asserted this directly maps to the claimed "agent that inhibits lysis of cells." Petitioner also mapped the dependent claims, arguing the references disclose using blood, plasma, and serum samples (claims 56-57, 62-63) and detecting polymorphisms or mutations (claims 66-67).
    • Motivation to Combine: A person of ordinary skill in the art (POSITA) would combine these references to solve a widely recognized problem. Petitioner argued that Lo explicitly noted the issue of "background maternal DNA" from lysed cells in serum samples, and Chiu's protocol suggested processing samples within two hours, implying degradation was a concern. A POSITA, faced with this known problem of assay interference, would have been motivated to look for known cell stabilization techniques. Bianchi provides a clear solution by teaching how to stabilize the very cells of interest (fetal cells in maternal blood) to prevent degradation.
    • Expectation of Success: A POSITA would have had a high expectation of success. The techniques of fetal DNA analysis (Chiu, Lo) and cell stabilization with formaldehyde (Bianchi) were both well-established. Combining them was a straightforward application of a known solution (stabilization) to a known problem (background noise from cell lysis) to predictably improve the outcome of a known process (fetal DNA detection).

Ground 2: Claims 55-63, 66-69, 80, and 127-132 are obvious over Chiu, Lo, and Rao.

  • Prior Art Relied Upon: Chiu (a 2001 article in Clinical Chemistry), Lo (a 1998 article in the American Journal of Human Genetics), and Rao (WO 03/018757).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground presented a parallel argument to Ground 1, substituting Rao for Bianchi. Petitioner again relied on Chiu and Lo for the foundational fetal DNA detection method. Rao was asserted to teach the use of a stabilizing agent to inhibit cell lysis in blood specimens containing rare cells. Rao discloses adding a stabilizer, such as an aldehyde (e.g., formaldehyde, glutaraldehyde) or a formaldehyde donor, directly into a blood collection tube. This directly teaches the claimed "agent." Petitioner highlighted that Rao is particularly relevant as it expressly includes pregnancy as a condition associated with rare cells in a biological specimen, directly linking its stabilization methods to the context of the ’277 patent.
    • Motivation to Combine: The motivation was again to improve the signal-to-noise ratio in fetal DNA detection. Given the problems of cell lysis identified by Lo and Chiu, a POSITA would be motivated to find a way to preserve sample integrity. Rao's method of stabilizing rare cells addresses an analogous problem. A POSITA would see Rao's technique as an advantageous alternative to the extra centrifugation or filtration steps suggested by Chiu, making the overall process more efficient and robust.
    • Expectation of Success: Petitioner argued that success would have been reasonably expected. The agents disclosed in Rao (e.g., aldehydes) were known to be effective cell stabilizers. A POSITA would expect that applying these agents to a maternal blood sample would predictably inhibit the lysis of maternal blood cells, thereby reducing background DNA and improving the accuracy of the fetal DNA quantification methods taught by Chiu and Lo.

4. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial under Fintiv would be inappropriate. It asserted that the parallel district court litigation had an uncertain trial date (July 2022) due to court backlogs, and that a Final Written Decision (FWD) from the Board could issue before the trial concludes. Petitioner also noted minimal investment in the parallel case and highlighted a stipulation filed in that case, promising not to pursue the same invalidity grounds at trial if the inter partes review (IPR) was instituted, thereby mitigating concerns of overlap and inefficiency.

5. Relief Requested

  • Petitioner requested institution of an IPR and cancellation of claims 55-63, 66-69, 80, and 127-132 of the ’277 patent as unpatentable under 35 U.S.C. §103.